This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gaboriau, F. Articles by Bolard, J. Search for Related Content PubMed PubMed Citation Articles by Gaboriau, F. Articles by Bolard, J.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother., Nov 1997, 2345-2351, Vol 41, No. 11
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

Heat-induced superaggregation of amphotericin B reduces its in vitro toxicity: a new way to improve its therapeutic index

F Gaboriau, M Cheron, C Petit and J Bolard
Laboratoire de Physicochimie Biomoleculaire et Cellulaire (CNRS UA 2056), Universite P. et M. Curie, Paris, France. gaboriau@wanadoo.fr

Superaggregation of amphotericin B (AmB) was previously shown to occur upon heating of solutions at 70 degrees C. In the present study, we demonstrate that heat pretreatment of Fungizone (deoxycholate salt of AmB [AmB-DOC]) solutions induces a drastic decrease in the in vitro toxicity of this antibiotic. Heated AmB-DOC colloidal solutions, which mainly contained superaggregated and monomeric forms of the antibiotic, were strongly less hemolytic than unheated solutions (aggregates and monomers). Thermal pretreatment of AmB-DOC solutions also reduced the toxicity to the cell line HT29, as deduced from two simultaneous cell viability assays (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release). These heated colloidal solutions were only slightly less efficient than the unheated ones at inhibiting the growth of Candida albicans cells in vitro. Such results suggest that mild heat treatment of AmB-DOC solutions could provide a new and simple solution for improving the therapeutic index of this antifungal agent by reducing its toxicity to mammalian cells.

This article has been cited by other articles:

• Bhattacharya, A., Mishra, L. C., Bhasin, V. K. (2008). In Vitro Activity of Artemisinin in Combination with Clotrimazole or Heat-treated Amphotericin B against Plasmodium falciparum. Am J Trop Med Hyg 78: 721-728 [Abstract] [Full Text]  
• Espada, R., Valdespina, S., Dea, M. A., Molero, G., Ballesteros, M. P., Bolas, F., Torrado, J. J. (2008). In vivo distribution and therapeutic efficacy of a novel amphotericin B poly-aggregated formulation. J Antimicrob Chemother 61: 1125-1131 [Abstract] [Full Text]  
• Hatabu, T., Takada, T., Taguchi, N., Suzuki, M., Sato, K., Kano, S. (2005). Potent Plasmodicidal Activity of a Heat-Induced Reformulation of Deoxycholate-Amphotericin B (Fungizone) against Plasmodium falciparum. Antimicrob. Agents Chemother. 49: 493-496 [Abstract] [Full Text]  
• Sanchez-Brunete, J. A., Dea, M. A., Rama, S., Bolas, F., Alunda, J. M., Raposo, R., Mendez, M. T., Torrado-Santiago, S., Torrado, J. J. (2004). Treatment of Experimental Visceral Leishmaniasis with Amphotericin B in Stable Albumin Microspheres. Antimicrob. Agents Chemother. 48: 3246-3252 [Abstract] [Full Text]  
• Bartlett, K., Yau, E., Hartsel, S. C., Hamer, A., Tsai, G., Bizzotto, D., Wasan, K. M. (2004). Effect of Heat-Treated Amphotericin B on Renal and Fungal Cytotoxicity. Antimicrob. Agents Chemother. 48: 333-336 [Abstract] [Full Text]  
• Cheron, M., Petit, C., Bolard, J., Gaboriau, F. (2003). Heat-induced reformulation of amphotericin B-deoxycholate favours drug uptake by the macrophage-like cell line J774. J Antimicrob Chemother 52: 904-910 [Abstract] [Full Text]  
• Espuelas, M. S., Legrand, P., Campanero, M. A., Appel, M., Cheron, M., Gamazo, C., Barratt, G., Irache, J. M. (2003). Polymeric carriers for amphotericin B: in vitro activity, toxicity and therapeutic efficacy against systemic candidiasis in neutropenic mice. J Antimicrob Chemother 52: 419-427 [Abstract] [Full Text]  
• Rogers, P. D., Barker, K. S., Herring, V., Jacob, M. (2003). Heat-induced superaggregation of amphotericin B attenuates its ability to induce cytokine and chemokine production in the human monocytic cell line THP-1. J Antimicrob Chemother 51: 405-408 [Abstract] [Full Text]  
• Dannaoui, E., Meis, J. F. G. M., Mouton, J. W., Verweij, P. E., the Eurofung Network, (2002). In vitro susceptibilities of Zygomycota to polyenes. J Antimicrob Chemother 49: 741-744 [Abstract] [Full Text]  
• Kwong, E. H., Ramaswamy, M., Bauer, E. A., Hartsel, S. C., Wasan, K. M. (2001). Heat Treatment of Amphotericin B Modifies Its Serum Pharmacokinetics, Tissue Distribution, and Renal Toxicity following Administration of a Single Intravenous Dose to Rabbits. Antimicrob. Agents Chemother. 45: 2060-2063 [Abstract] [Full Text]  
• van Etten, E. W. M., van Vianen, W., Roovers, P., Frederik, P. (2000). Mild Heating of Amphotericin B-Desoxycholate: Effects on Ultrastructure, In Vitro Activity and Toxicity, and Therapeutic Efficacy in Severe Candidiasis in Leukopenic Mice. Antimicrob. Agents Chemother. 44: 1598-1603 [Abstract] [Full Text]  
• Petit, C., Yardley, V., Gaboriau, F., Bolard, J., Croft, S. L. (1999). Activity of a Heat-Induced Reformulation of Amphotericin B Deoxycholate (Fungizone) against Leishmania donovani. Antimicrob. Agents Chemother. 43: 390-392 [Abstract] [Full Text]